evobrutinib   Click here for help

GtoPdb Ligand ID: 9752

Synonyms: A250 [WO2012170976] | M-2951 | M2951 | MSC 2364447 | MSC-2364447C | MSC2364447C
PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Evobrutinib is a Bruton's tyrosine kinase Inhibitor discovered by Merck, that has clinical potential across multiple autoimmune conditions (including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis) [1]. it is an orally active, potent, and highly selective inhibitor with a covalent binding mode. The chemical structure is claimed as A250 in patent WO2012170976 [3].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 6
Hydrogen bond donors 2
Rotatable bonds 8
Topological polar surface area 93.37
Molecular weight 429.22
XLogP 4.11
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES C=CC(=O)N1CCC(CC1)CNc1ncnc(c1c1ccc(cc1)Oc1ccccc1)N
Isomeric SMILES C=CC(=O)N1CCC(CC1)CNc1ncnc(c1c1ccc(cc1)Oc1ccccc1)N
InChI InChI=1S/C25H27N5O2/c1-2-22(31)30-14-12-18(13-15-30)16-27-25-23(24(26)28-17-29-25)19-8-10-21(11-9-19)32-20-6-4-3-5-7-20/h2-11,17-18H,1,12-16H2,(H3,26,27,28,29)
InChI Key QUIWHXQETADMGN-UHFFFAOYSA-N
Immunopharmacology Comments
Evobrutinib is a selective BTK inhibitor that potently inhibits B cell receptor- and Fc receptor-mediated signaling and downstream activation/function of human B cells and innate immune cells (e.g. monocytes and basophils). It has therapeutic potential for the management of B cell-driven autoimmune conditions [2].
Immunopharmacology Disease
Disease X-Refs Comment References
Rheumatoid arthritis Disease Ontology: DOID:7148
OMIM: 180300
 Phase 2 clinical candidate for RA- see NCT03233230
Systemic lupus erythematosus Disease Ontology: DOID:9074
OMIM: 152700
Orphanet: ORPHA536
 Phase 2 clinical candidate for SLE- see NCT02975336
Relapsing-remitting multiple sclerosis Disease Ontology: DOID:2378
 Phase 3 clinical candidate for RR-MS- see NCT04032171 and NCT04032158. Positive Phase 2 results (from NCT02975349) are reported in Montalban et al., 2019. In this study once daily evobrutinib (75 mg) reduced the number of gadolinium-enhancing lesions significantly more than placebo. 4